The efficient utilization of rice waste has the potential to significantly contribute to environmental sustainability by minimizing the waste impact on the environment. Through repurposing such waste, novel materials can be developed for various biomedical applications. This approach not only mitigates waste, but it also promotes the adoption of sustainable materials within the industry. In this research, rice-straw-derived nanofibers (RSNFs) were utilized as a reinforcement material for high-density polyethylene (HDPE). The rice-straw-derived nanofibers were incorporated at different concentrations (1, 2, 3, and 4 wt.%) into the HDPE. The composites were fabricated using twin-screw extrusion (to ensure homogenous distribution) and the injection-molding process (to crease the test samples). Then, the mechanical strengths and frictional performances of the bio-composites were assessed. Different characterization techniques were utilized to investigate the morphology of the RSNFs. Thermal analyses (TGA/DTG/DSC), the contact angle, and XRD were utilized to study the performances of the HDPE/RSNF composites. The study findings demonstrated that the addition of RSNFs as a reinforcement to the HDPE improved the hydrophilicity, strength, hardness, and wear resistance of the proposed bio-composites.